Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder.

There is significant clinical heterogeneity in language and communication abilities of individuals with Autism Spectrum Disorders (ASD). However, no consistent pathology regarding the relationship of these abilities to brain structure has emerged. Recent developments in anatomical correlation-based approaches to map structural covariance networks (SCNs), combined with detailed behavioral characterization, offer an alternative for studying these relationships. In this study, such an approach was used to study the integrity of SCNs of cortical thickness and surface area associated with language and communication, in 46 high-functioning, school-age children with ASD compared with 50 matched, typically developing controls (all males) with IQ > 75. Findings showed that there was alteration of cortical structure and disruption of fronto-temporal cortical covariance in ASD compared with controls. Furthermore, in an analysis of a subset of ASD participants, alterations in both cortical structure and covariance were modulated by structural language ability of the participants, but not communicative function. These findings indicate that structural language abilities are related to altered fronto-temporal cortical covariance in ASD, much more than symptom severity or cognitive ability. They also support the importance of better characterizing ASD samples while studying brain structure and for better understanding individual differences in language and communication abilities in ASD.

Auditory Pitch Perception in Autism Spectrum Disorder Is Associated With Nonverbal Abilities.

Atypical sensory perception and heterogeneous cognitive profiles are common features of autism spectrum disorder (ASD). However, previous findings on auditory sensory processing in ASD are mixed. Accordingly, auditory perception and its relation to cognitive abilities in ASD remain poorly understood. Here, children with ASD, and age- and intelligence quotient (IQ)-matched typically developing children, were tested on a low- and a higher level pitch processing task. Verbal and nonverbal cognitive abilities were measured using the Wechsler's Abbreviated Scale of Intelligence. There were no group differences in performance on either auditory task or IQ measure. However, there was significant variability in performance on the auditory tasks in both groups that was predicted by nonverbal, not verbal skills. These results suggest that auditory perception is related to nonverbal reasoning rather than verbal abilities in ASD and typically developing children. In addition, these findings provide evidence for preserved pitch processing in school-age children with ASD with average IQ, supporting the idea that there may be a subgroup of individuals with ASD that do not present perceptual or cognitive difficulties. Future directions involve examining whether similar perceptual-cognitive relationships might be observed in a broader sample of individuals with ASD, such as those with language impairment or lower IQ.

Insertion of i-gel™ by the reversed technique improves the success rate and reduces the time taken for its placement: A prospective, randomized, controlled, interventional trial.

BACKGROUND AND AIMS: We hypothesized that the i-gel™ supra-glottic airway can be inserted with relative ease in a reversed manner just like a Guedel's airway. MATERIAL AND METHODS: A prospective, randomized, controlled interventional trial was conducted on 100 patients to compare reversed insertion of the i-gel™ (Group R) with the conventional insertion (Group C). In Group C, i-gel™ was introduced in a conventional manner, whereas in the Group R, i-gel™ was introduced into the oral cavity with the concavity facing the hard palate. On reaching the oropharynx, the device was rotated 180° and advanced further until it fitted over the larynx. The time of insertion, ease, and placement appropriateness were compared. RESULTS: All patients completed the study. Better success rate of the first attempt insertion was achieved using the reversed technique (96% vs. 86%), but it was not statistically significant. Mean time required for i-gel™ insertion in Group R was 17.5 ± 6.9 s as compared to 20.8 ± 5.9 s in Group C, which was statistically significant. In Group R, it could be inserted within 20 s in 84% of cases, but only in 62% in Group C. The seal of the i-gel™ was similar in both the groups with the leak volumes (inspired - expired tidal volumes) being similar. CONCLUSION: Reversed insertion technique for the placement of i-gel™ resulted in appropriate placement with easier insertion and lower placement time than that with the conventional technique.

Response to Music-Mediated Intervention in Autistic Children with Limited Spoken Language Ability.

PURPOSE: Autistic children with limited spoken language ability (LSLA) often do not respond to traditional interventions, reducing their social inclusion. It is essential to identify effective interventions, and sensitive measures to track their intervention response. METHODS: Using data from an RCT comparing music-mediated and play-based interventions, we investigated the impact of spoken language ability on outcomes, and measured response to intervention through natural language sample measures. RESULTS: Children with lower verbal IQ, relative to higher verbal IQ, made some greater gains over the course of music-mediated intervention. Natural language samples were helpful in characterizing communication and tracking change. CONCLUSION: Music-mediated interventions hold promise as effective interventions for autistic children with LSLA. Natural language samples are robust in characterizing this subgroup.

Enhanced Memory for Vocal Melodies in Autism Spectrum Disorder and Williams Syndrome.

Adults and children with typical development (TD) remember vocal melodies (without lyrics) better than instrumental melodies, which is attributed to the biological and social significance of human vocalizations. Here we asked whether children with autism spectrum disorder (ASD), who have persistent difficulties with communication and social interaction, and adolescents and adults with Williams syndrome (WS), who are highly sociable, even indiscriminately friendly, exhibit a memory advantage for vocal melodies like that observed in individuals with TD. We tested 26 children with ASD, 26 adolescents and adults with WS of similar mental age, and 26 children with TD on their memory for vocal and instrumental (piano, marimba) melodies. After exposing them to 12 unfamiliar folk melodies with different timbres, we required them to indicate whether each of 24 melodies (half heard previously) was old (heard before) or new (not heard before) during an unexpected recognition test. Although the groups successfully distinguished the old from the new melodies, they differed in overall memory. Nevertheless, they exhibited a comparable advantage for vocal melodies. In short, individuals with ASD and WS show enhanced processing of socially significant auditory signals in the context of music. LAY SUMMARY: Typically developing children and adults remember vocal melodies better than instrumental melodies. In this study, we found that children with Autistic Spectrum Disorder, who have severe social processing deficits, and children and adults with Williams syndrome, who are highly sociable, exhibit comparable memory advantages for vocal melodies. The results have implications for musical interventions with these populations.

Joint engagement and movement: Active ingredients of a music-based intervention with school-age children with autism.

BACKGROUND: The effectiveness of music-based interventions (MI) in autism has been attested for decades. Yet, there has been little empirical investigation of the active ingredients, or processes involved in music-based interventions that differentiate them from other approaches. OBJECTIVES: Here, we examined whether two processes, joint engagement and movement, which have previously been studied in isolation, contribute as important active ingredients for the efficacy of music-based interventions. METHODS: In two separate analyses, we investigated whether (1) joint engagement with the therapist, measured using a coding scheme verified for reliability, and (2) movement elicited by music-making, measured using a computer-vision technique for quantifying motion, may drive the benefits previously observed in response to MI (but not a controlled non-MI) in children with autism. RESULTS: Compared to a non-music control intervention, children and the therapist in MI spent more time in triadic engagement (between child, therapist, and activity) and produced greater movement, with amplitude of motion closely linked to the type of musical instrument. CONCLUSIONS: Taken together, these findings provide initial evidence of the active ingredients of music-based interventions in autism.

Towards greater transparency in neurodevelopmental disorders research: use of a proposed workflow and propensity scores to facilitate selection of matched groups.

BACKGROUND: Matching is one commonly utilized method in quasi-experimental designs involving individuals with neurodevelopmental disorders (NDD). This method ensures two or more groups (e.g., individuals with an NDD versus neurotypical individuals) are balanced on pre-existing covariates (e.g., IQ), enabling researchers to interpret performance on outcome measures as being attributed to group membership. While much attention has been paid to the statistical criteria of how to assess whether groups are well-matched, relatively little attention has been given to a crucial prior step: the selection of the individuals that are included in matched groups. The selection of individuals is often an undocumented process, which can invite unintentional, arbitrary, and biased decision-making. Limited documentation can result in findings that have limited reproducibility and replicability and thereby have poor potential for generalization to the broader population. Especially given the heterogeneity of individuals with NDDs, interpretation of research findings depends on minimizing bias at all stages of data collection and analysis. RESULTS: In the spirit of open science, this tutorial demonstrates how a workflow can be used to provide a transparent, reproducible, and replicable process to select individuals for matched groups. Our workflow includes the following key steps: Assess data, Select covariates, Conduct matching, and Diagnose matching. Our sample dataset is from children with autism spectrum disorder (ASD; n = 25) and typically developing children (n = 43) but can be adapted to comparisons of any two groups in quasi-experimental designs. We work through this method to conduct and document matching using propensity scores implemented with the R package MatchIt. Data and code are publicly available, and a template for this workflow is provided in the Additional file 1 as well as on a public repository. CONCLUSIONS: It is important to provide clear documentation regarding the selection process to establish matched groups. This documentation ensures better transparency in participant selection and data analysis in NDD research. We hope the adoption of such a workflow will ultimately advance our ability to replicate findings and help improve the lives of individuals with NDDs.

What Makes Musical Prodigies?

Musical prodigies reach exceptionally high levels of achievement before adolescence. Despite longstanding interest and fascination in musical prodigies, little is known about their psychological profile. Here we assess to what extent practice, intelligence, and personality make musical prodigies a distinct category of musician. Nineteen former or current musical prodigies (aged 12-34) were compared to 35 musicians (aged 14-37) with either an early (mean age 6) or late (mean age 10) start but similar amount of musical training, and 16 non-musicians (aged 14-34). All completed a Wechsler IQ test, the Big Five Inventory, the Autism Spectrum Quotient, the Barcelona Music Reward Questionnaire, the Dispositional Flow Scale, and a detailed history of their lifetime music practice. None of the psychological traits distinguished musical prodigies from control musicians or non-musicians except their propensity to report flow during practice. The other aspects that differentiated musical prodigies from their peers were the intensity of their practice before adolescence, and the source of their motivation when they began to play. Thus practice, by itself, does not make a prodigy. The results are compatible with multifactorial models of expertise, with prodigies lying at the high end of the continuum. In summary, prodigies are expected to present brain predispositions facilitating their success in learning an instrument, which could be amplified by their early and intense practice happening at a moment when brain plasticity is heightened.

Wired for musical rhythm? A diffusion MRI-based study of individual differences in music perception.

Music perceptual abilities are subjective and exhibit high inter-individual variability. Twenty-nine participants with varying degrees of musical training were tested for musical perception ability with the Profile of Music Perception Skills (PROMS) and brain structural measures obtained via diffusion tensor imaging. Controlling for the period of training, TBSS results showed that individuals with better musical perception abilities showed increased deviations from linear anisotropy in the corpus callosum. Specifically, mode of anisotropy in the genu and body of the corpus callosum was negatively correlated with music perception score suggesting the presence of crossing fibers. A multi-compartment model of crossing fibers revealed a significant positive relation for partial volumes of secondary fiber populations with timing aspects of music perception. Our results suggest that inter-hemispheric connectivity differences in the anterior parts of the corpus callosum may reflect innate differences in the processing of the rhythmic aspects of music.

Pitch direction ability predicts melodic perception in autism.

Individuals with autism spectrum disorders (ASDs) often present atypical auditory perception. Previous work has reported both enhanced low-level pitch discrimination and superior abilities to detect local pitch structure on higher-level melodic tasks in ASD. However, it is unclear how low and high levels of auditory perception are related in ASD or typical development (TD), or how this relationship might change across development and stimulus presentation rates. To these aims, in the present study, children with ASD and TD were tested on a low-level pitch direction discrimination task and a high-level melodic global-local task. Groups performed similarly on both of these auditory tasks. Moreover, individual differences in low-level pitch direction ability predicted performance on the higher-level global-local task, with a stronger relationship in ASD. Age did not affect the relationship between low-level and high-level pitch performance in either ASD or TD. However, there was a more positive effect of age on the high-level global-local task performance in TD than ASD. Finally, there was no effect of stimulus rate on the relationship between low-level and high-level pitch performance in either group. These findings provide a better understanding of how perception is associated across levels of processing in ASD versus TD. This work helps to better understand individual differences in auditory perception and to refine ASD phenotypes.

Speech perception in autism spectrum disorder: An activation likelihood estimation meta-analysis.

Autism spectrum disorder (ASD) is often characterized by atypical language profiles and auditory and speech processing. These can contribute to aberrant language and social communication skills in ASD. The study of the neural basis of speech perception in ASD can serve as a potential neurobiological marker of ASD early on, but mixed results across studies renders it difficult to find a reliable neural characterization of speech processing in ASD. To this aim, the present study examined the functional neural basis of speech perception in ASD versus typical development (TD) using an activation likelihood estimation (ALE) meta-analysis of 18 qualifying studies. The present study included separate analyses for TD and ASD, which allowed us to examine patterns of within-group brain activation as well as both common and distinct patterns of brain activation across the ASD and TD groups. Overall, ASD and TD showed mostly common brain activation of speech processing in bilateral superior temporal gyrus (STG) and left inferior frontal gyrus (IFG). However, the results revealed trends for some distinct activation in the TD group showing additional activation in higher-order brain areas including left superior frontal gyrus (SFG), left medial frontal gyrus (MFG), and right IFG. These results provide a more reliable neural characterization of speech processing in ASD relative to previous single neuroimaging studies and motivate future work to investigate how these brain signatures relate to behavioral measures of speech processing in ASD.

Music improves social communication and auditory-motor connectivity in children with autism.

Music has been identified as a strength in people with Autism Spectrum Disorder; however, there is currently no neuroscientific evidence supporting its benefits. Given its universal appeal, intrinsic reward value and ability to modify brain and behaviour, music may be a potential therapeutic aid in autism. Here we evaluated the neurobehavioural outcomes of a music intervention, compared to a non-music control intervention, on social communication and brain connectivity in school-age children (ISRCTN26821793). Fifty-one children aged 6-12 years with autism were randomized to receive 8-12 weeks of music (n = 26) or non-music intervention (n = 25). The music intervention involved use of improvisational approaches through song and rhythm to target social communication. The non-music control was a structurally matched behavioural intervention implemented in a non-musical context. Groups were assessed before and after intervention on social communication and resting-state functional connectivity of fronto-temporal brain networks. Communication scores were higher in the music group post-intervention (difference score = 4.84, P = .01). Associated post-intervention resting-state brain functional connectivity was greater in music vs. non-music groups between auditory and subcortical regions (z = 3.94, P < .0001) and auditory and fronto-motor regions (z = 3.16, P < .0001). Post-intervention brain connectivity was lower between auditory and visual regions in the music compared to the non-music groups, known to be over-connected in autism (z = 4.01, P < .00001). Post-intervention brain connectivity in the music group was related to communication improvement (z = 3.57, P < .0001). This study provides the first evidence that 8-12 weeks of individual music intervention can indeed improve social communication and functional brain connectivity, lending support to further investigations of neurobiologically motivated models of music interventions in autism.

Disruption of structural covariance networks for language in autism is modulated by verbal ability.

The presence of widespread speech and language deficits is a core feature of autism spectrum disorders (ASD). These impairments have often been attributed to altered connections between brain regions. Recent developments in anatomical correlation-based approaches to map structural covariance offer an effective way of studying such connections in vivo. In this study, we employed such a structural covariance network (SCN)-based approach to investigate the integrity of anatomical networks in fronto-temporal brain regions of twenty children with ASD compared to an age and gender-matched control group of twenty-two children. Our findings reflected large-scale disruption of inter and intrahemispheric covariance in left frontal SCNs in the ASD group compared to controls, but no differences in right fronto-temporal SCNs. Interhemispheric covariance in left-seeded networks was further found to be modulated by verbal ability of the participants irrespective of autism diagnosis, suggesting that language function might be related to the strength of interhemispheric structural covariance between frontal regions. Additionally, regional cortical thickening was observed in right frontal and left posterior regions, which was predicted by decreasing symptom severity and increasing verbal ability in ASD. These findings unify reports of regional differences in cortical morphology in ASD. They also suggest that reduced left hemisphere asymmetry and increased frontal growth may not only reflect neurodevelopmental aberrations but also compensatory mechanisms.

Imaging Brain Development: Benefiting from Individual Variability.

Human brain development is a complex process that evolves from early childhood to young adulthood. Major advances in brain imaging are increasingly being used to characterize the developing brain. These advances have further helped to elucidate the dynamic maturational processes that lead to the emergence of complex cognitive abilities in both typical and atypical development. However, conventional approaches involve categorical group comparison models and tend to disregard the role of widespread interindividual variability in brain development. This review highlights how this variability can inform our understanding of developmental processes. The latest studies in the field of brain development are reviewed, with a particular focus on the role of individual variability and the consequent heterogeneity in brain structural and functional development. This review also highlights how such heterogeneity might be utilized to inform our understanding of complex neuropsychiatric disorders and recommends the use of more dimensional approaches to study brain development.

Fronto-temporal connectivity is preserved during sung but not spoken word listening, across the autism spectrum.

Co-occurrence of preserved musical function with language and socio-communicative impairments is a common but understudied feature of Autism Spectrum Disorders (ASD). Given the significant overlap in neural organization of these processes, investigating brain mechanisms underlying speech and music may not only help dissociate the nature of these auditory processes in ASD but also provide a neurobiological basis for development of interventions. Using a passive-listening functional magnetic resonance imaging paradigm with spoken words, sung words and piano tones, we found that 22 children with ASD, with varying levels of functioning, activated bilateral temporal brain networks during sung-word perception, similarly to an age and gender-matched control group. In contrast, spoken-word perception was right-lateralized in ASD and elicited reduced inferior frontal gyrus (IFG) activity which varied as a function of language ability. Diffusion tensor imaging analysis reflected reduced integrity of the left hemisphere fronto-temporal tract in the ASD group and further showed that the hypoactivation in IFG was predicted by integrity of this tract. Subsequent psychophysiological interactions revealed that functional fronto-temporal connectivity, disrupted during spoken-word perception, was preserved during sung-word listening in ASD, suggesting alternate mechanisms of speech and music processing in ASD. Our results thus demonstrate the ability of song to overcome the structural deficit for speech across the autism spectrum and provide a mechanistic basis for efficacy of song-based interventions in ASD.

The effect of sung speech on socio-communicative responsiveness in children with autism spectrum disorders.

There is emerging evidence to demonstrate the efficacy of music-based interventions for improving social functioning in children with Autism Spectrum Disorders (ASD). While this evidence lends some support in favor of using song over spoken directives in facilitating engagement and receptive intervention in ASD, there has been little research that has investigated the efficacy of such stimuli on socio-communicative responsiveness measures. Here, we present preliminary results from a pilot study which tested whether sung instruction, as compared to spoken directives, could elicit greater number of socio-communicative behaviors in young children with ASD. Using an adapted single-subject design, three children between the ages of 3 and 4 years, participated in a programme consisting of 18 sessions, of which 9 were delivered with spoken directives and 9 with sung. Sessions were counterbalanced and randomized for three play activities-block matching, picture matching and clay play. All sessions were video-recorded for post-hoc observational coding of three behavioral metrics which included performance, frequency of social gesture and eye contact. Analysis of the videos by two independent raters indicated increased socio-communicative responsiveness in terms of frequency of social gesture as well as eye contact during sung compared to spoken conditions, across all participants. Our findings suggest that sung directives may play a useful role in engaging children with ASD and also serve as an effective interventional medium to enhance socio-communicative responsiveness.

A novel method for assessing the development of speech motor function in toddlers with autism spectrum disorders.

There is increasing evidence to show that indicators other than socio-cognitive abilities might predict communicative function in Autism Spectrum Disorders (ASD). A potential area of research is the development of speech motor function in toddlers. Utilizing a novel measure called "articulatory features," we assess the abilities of toddlers to produce sounds at different timescales as a metric of their speech motor skills. In the current study, we examined (1) whether speech motor function differed between toddlers with ASD, developmental delay (DD), and typical development (TD); and (2) whether differences in speech motor function are correlated with standard measures of language in toddlers with ASD. Our results revealed significant differences between a subgroup of the ASD population with poor verbal skills, and the other groups, for the articulatory features associated with the shortest-timescale, namely place of articulation (POA), (p < 0.05). We also found significant correlations between articulatory features and language and motor ability as assessed by the Mullen and the Vineland scales for the ASD group. Our findings suggest that articulatory features may be an additional measure of speech motor function that could potentially be useful as an early risk indicator of ASD.

Sounds of melody--pitch patterns of speech in autism.

The objective of this study was to find a pattern in vocalizations of children with Autism Spectrum Disorder (ASD). We compared the intonational features of 15 children with ASD who showed speech, aged 4-10 years, with 10 age-matched typically developing controls. Exaggerated pitch, pitch range, pitch excursion and pitch contours were observed in speech of children with autism, but absent in age-matched controls. These exaggerated features, which are distinctive characteristics of motherese, were also seen in interactions of an independent group of 8 mothers of typical infants using child-directed speech. Our findings provide the first evidence of a distinct pattern in vocal output from children with autism. They also demonstrate that speech patterns might follow a delayed developmental trajectory in these children.